Modified Valsalva manoeuvre to treat recurrent supraventricular tachycardia: description of the technique and its successful use in a patient with a previous near fatal complication of DC cardioversion

Patients with attacks of re-entrant supraventricular tachycardia (SVT) frequently present to the emergency department (ED). The Valsalva manoeuvre (VM) is the most effective and safe vagal manoeuvre and advocated as the first-line treatment in stable patients but has a relatively low cardioversion success rate. Improving its efficacy would reduce patients' exposure to the side effects and complications of second-line treatments and has other potential benefits. We describe a modification to the VM, which is currently being studied, and present the case of a 23-year-old patient who was successfully treated with this modified VM after a previous near-fatal complication of direct current (DC) cardioversion.RD&E staff can access the full-text of this article by clicking on the 'Additional Link' above and logging in with NHS OpenAthens if prompted

Randomised Evaluation of Modified Valsalva Effectiveness in Re-Entrant Tachycardias (REVERT)

Conference posterThe Valsalva manoeuvre is an internationally recommended physical emergency treatment for supraventricular tachycardia (SVT), an abnormal fast heart rhythm. However in normal practice, the manoeuvre only works in 5–20% of cases and intravenous treatment with adenosine is required. This drug causes a pause in heart activity which patients often find very distressing. A simple posture modification to the Valsalva manoeuvre could improve its effectiveness and we carried out a randomised controlled trial to assess whether it could increase the rate of cardioversion and reduce use of adenosine.REVERT is funded by the National Institute for Health Research (NIHR) through its Research for Patient Benefit (RfPB) Programme: Grant Reference Number PB-PG-0211-24145. The study has been approved by the South West Exeter Research Ethics Committee, is registered with Current Controlled Trials (ISRCTN67937027) and has been adopted by the NIHR Clinical Research Network

Postural modification to the standard Valsalva manoeuvre for emergency treatment of supraventricular tachycardias (REVERT): a randomised controlled trial

BACKGROUND: The Valsalva manoeuvre is an internationally recommended treatment for supraventricular tachycardia, but cardioversion is rare in practice (5-20%), necessitating the use of other treatments including adenosine, which patients often find unpleasant. We assessed whether a postural modification to the Valsalva manoeuvre could improve its effectiveness. METHODS: We did a randomised controlled, parallel-group trial at emergency departments in England. We randomly allocated adults presenting with supraventricular tachycardia (excluding atrial fibrillation and flutter) in a 1:1 ratio to undergo a modified Valsalva manoeuvre (done semi-recumbent with supine repositioning and passive leg raise immediately after the Valsalva strain), or a standard semi-recumbent Valsalva manoeuvre. A 40 mm Hg pressure, 15 s standardised strain was used in both groups. Randomisation, stratified by centre, was done centrally and independently, with allocation with serially numbered, opaque, sealed, tamper-evident envelopes. Patients and treating clinicians were not masked to allocation. The primary outcome was return to sinus rhythm at 1 min after intervention, determined by the treating clinician and electrocardiogram and confirmed by an investigator masked to treatment allocation. This study is registered with Current Controlled Trials (ISRCTN67937027). FINDINGS: We enrolled 433 participants between Jan 11, 2013, and Dec 29, 2014. Excluding second attendance by five participants, 214 participants in each group were included in the intention-to-treat analysis. 37 (17%) of 214 participants assigned to standard Valsalva manoeuvre achieved sinus rhythm compared with 93 (43%) of 214 in the modified Valsalva manoeuvre group (adjusted odds ratio 3.7 (95% CI 2.3-5.8; p<0.0001). We recorded no serious adverse events. INTERPRETATION: In patients with supraventricular tachycardia, a modified Valsalva manoeuvre with leg elevation and supine positioning at the end of the strain should be considered as a routine first treatment, and can be taught to patients. FUNDING: National Institute for Health Research.This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text

The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF): feasibility trial protocol

Background: Topical lidocaine patches, applied over rib fractures, have been suggested as a non-invasive method of local anaesthetic delivery to improve respiratory function, reduce opioid consumption and consequently reduce pulmonary complications. Older patients may gain most benefit from improved analgesic regimens yet lidocaine patches are untested as an early intervention in the Emergency Department (ED). The aim of this trial is to investigate uncertainties around trial design and conduct, to establish whether a definitive randomised trial of topical lidocaine patches in older patients with rib fractures is feasible. Methods: RELIEF is an open label, multicentre, parallel group, individually randomised, feasibility randomised controlled trial with economic scoping and nested qualitative study. Patients aged ≥ 65 years presenting to the ED with traumatic rib fracture(s) requiring admission will be randomised 1:1 to lidocaine patches (intervention), in addition to standard clinical management, or standard clinical management alone. Lidocaine patches will be applied immediately after diagnosis in ED and continued daily for 72 hours or until discharge. Feasibility outcomes will focus on recruitment, adherence and follow-up data with a total sample size of 100. Clinical outcomes, such as 30-day pulmonary complications, and resource use will be collected to understand feasibility of data collection. Qualitative interviews will explore details of the trial design, trial acceptability and recruitment processes. An evaluation of the feasibility of measuring health economics outcomes data will be completed. Discussion: Interventions to improve outcomes in elderly patients with rib fractures are urgently required. This feasibility trial will test a novel early intervention which has the potential of fulfilling this unmet need. The Randomised Evaluation of early topical Lidocaine patches In Elderly patients admitted to hospital with rib Fractures (RELIEF) feasibility trial will determine whether a definitive trial is feasible. ISRCTN Registration: ISRCTN14813929 (22/04/2021)

Predicting outcomes after blunt chest wall trauma: development and external validation of a new prognostic model. Crit Care 2014;18:R98

in press). Predicting outcomes after blunt chest wall trauma: development and external validation of a new prognostic model. Critical Care, 18(R98) http://dx.doi.org/doi:10.1186/cc13873 _____________________________________________________________ This article is brought to you by Swansea University. Any person downloading material is agreeing to abide by the terms of the repository licence. Authors are personally responsible for adhering to publisher restrictions or conditions. When uploading content they are required to comply with their publisher agreement and the SHERPA RoMEO database to judge whether or not it is copyright safe to add this version of the paper to this repository. Abstract Introduction: Blunt chest wall trauma accounts for over 15% of all trauma admissions to Emergency Departments worldwide. Reported mortality rates vary between 4 and 60%. Management of this patient group is challenging as a result of the delayed on-set of complications. The aim of this study was to develop and validate a prognostic model that can be used to assist in the management of blunt chest wall trauma. Methods: There were two distinct phases to the overall study; the development and the validation phases. In the first study phase, the prognostic model was developed through the retrospective analysis of all blunt chest wall trauma patients (n = 274) presenting to the Emergency Department of a regional trauma centre in Wales (2009 to 2011). Multivariable logistic regression was used to develop the model and identify the significant predictors for the development of complications. The model&apos;s accuracy and predictive capabilities were assessed. In the second study phase, external validation of the model was completed in a multi-centre prospective study (n = 237) in 2012. The model&apos;s accuracy and predictive capabilities were re-assessed for the validation sample. A risk score was developed for use in the clinical setting. Results: Significant predictors of the development of complications were age, number of rib fractures, chronic lung disease, use of pre-injury anticoagulants and oxygen saturation levels. The final model demonstrated an excellent c-index of 0.96 (95% confidence intervals: 0.93 to 0.98). Conclusions: In our two phase study, we have developed and validated a prognostic model that can be used to assist in the management of blunt chest wall trauma patients. The final risk score provides the clinician with the probability of the development of complications for each individual patient

Precision oncology using ex vivo technology: a step towards individualised cancer care?

Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes

Ex-vivo drug screening of surgically resected glioma stem cells to replace murine avatars and provide personalise cancer therapy for glioblastoma patients

With diminishing returns and high clinical failure rates from traditional preclinical and animal-based drug discovery strategies, more emphasis is being placed on alternative drug discovery platforms. Ex vivo approaches represent a departure from both more traditional preclinical animal-based models and clinical-based strategies and aim to address intra-tumoural and inter-patient variability at an earlier stage of drug discovery. Additionally, these approaches could also offer precise treatment stratification for patients within a week of tumour resection in order to direct tailored therapy. One tumour group that could significantly benefit from such ex vivo approaches are high-grade gliomas, which exhibit extensive heterogeneity, cellular plasticity and therapy-resistant glioma stem cell (GSC) niches. Historic use of murine-based preclinical models for these tumours has largely failed to generate new therapies, resulting in relatively stagnant and unacceptable survival rates of around 12-15 months post-diagnosis over the last 50 years. The near universal use of DNA damaging chemoradiotherapy after surgical resection within standard-of-care (SoC) therapy regimens provides an opportunity to improve current treatments if we can identify efficient drug combinations in preclinical models that better reflect the complex inter-/intra-tumour heterogeneity, GSC plasticity and inherent DNA damage resistance mechanisms. We have therefore developed and optimised a high-throughput ex vivo drug screening platform; GliExP, which maintains GSC populations using immediately dissociated fresh surgical tissue. As a proof-of-concept for GliExP, we have optimised SoC therapy responses and screened 30+ small molecule therapeutics and preclinical compounds against tumours from 18 different patients, including multi-region spatial heterogeneity sampling from several individual tumours. Our data therefore provides a strong basis to build upon GliExP to incorporate combination-based oncology therapeutics in tandem with SoC therapies as an important preclinical alternative to murine models (reduction and replacement) to triage experimental therapeutics for clinical translation and deliver rapid identification of effective treatment strategies for individual gliomas

Ex-vivo drug screening of surgically resected glioma stem cells to replace murine avatars and provide personalise cancer therapy for glioblastoma patients [version 1; peer review: 2 approved]

With diminishing returns and high clinical failure rates from traditional preclinical and animal-based drug discovery strategies, more emphasis is being placed on alternative drug discovery platforms. Ex vivo approaches represent a departure from both more traditional preclinical animal-based models and clinical-based strategies and aim to address intra-tumoural and inter-patient variability at an earlier stage of drug discovery. Additionally, these approaches could also offer precise treatment stratification for patients within a week of tumour resection in order to direct tailored therapy. One tumour group that could significantly benefit from such ex vivo approaches are high-grade gliomas, which exhibit extensive heterogeneity, cellular plasticity and therapy-resistant glioma stem cell (GSC) niches. Historic use of murine-based preclinical models for these tumours has largely failed to generate new therapies, resulting in relatively stagnant and unacceptable survival rates of around 12-15 months post-diagnosis over the last 50 years. The near universal use of DNA damaging chemoradiotherapy after surgical resection within standard-of-care (SoC) therapy regimens provides an opportunity to improve current treatments if we can identify efficient drug combinations in preclinical models that better reflect the complex inter-/intra-tumour heterogeneity, GSC plasticity and inherent DNA damage resistance mechanisms. We have therefore developed and optimised a high-throughput ex vivo drug screening platform; GliExP, which maintains GSC populations using immediately dissociated fresh surgical tissue. As a proof-of-concept for GliExP, we have optimised SoC therapy responses and screened 30+ small molecule therapeutics and preclinical compounds against tumours from 18 different patients, including multi-region spatial heterogeneity sampling from several individual tumours. Our data therefore provides a strong basis to build upon GliExP to incorporate combination-based oncology therapeutics in tandem with SoC therapies as an important preclinical alternative to murine models (reduction and replacement) to triage experimental therapeutics for clinical translation and deliver rapid identification of effective treatment strategies for individual gliomas

A multicentre randomised feasibility STUdy evaluating the impact of a prognostic model for management of BLunt chest wall trauma patients : STUMBL Trial

Objective: A new prognostic model has been developed and externally validated, the aim of which is to assist in the management of the blunt chest wall trauma patient in the emergency department (ED). The aim of this trial is to assess the feasibility and acceptability of a definitive impact trial investigating the clinical and cost-effectiveness of a new prognostic model for the management of patients with blunt chest wall trauma in the ED. Design: Stepped wedge feasibility trial. Setting: Four EDs in England and Wales. Participants: Adult blunt chest wall trauma patients presenting to the ED with no concurrent, life-threatening injuries. Intervention: A prognostic model (the STUMBL score) to guide clinical decision-making. Outcome measures: Primary: participant recruitment rate and clinicians’ use of the STUMBL score. Secondary: composite outcome measure (mortality, pulmonary complications, delayed upgrade in care, unplanned representations to the ED), physical and mental components of quality of life, clinician feedback and health economic data gathering methodology for healthcare resource utilisation. Results: Quantitative data were analysed using the intention-to-treat principle. 176 patients were recruited; recruitment targets were achieved at all sites. Clinicians used the model in 96% of intervention cases. All feasibility criteria were fully or partially met. After adjusting for predefined covariates, there were no statistically significant differences between the control and intervention periods. Qualitative analysis highlighted that STUMBL was well-received and clinicians would support a definitive trial. Collecting data on intervention costs, health-related quality of life and healthcare resource use was feasible. Discussion: We have demonstrated that a fully powered randomised clinical trial of the STUMBL score is feasible and desirable to clinicians. Minor methodological modifications will be made for the full trial. Trial registration number: ISRCTN95571506; Post-results